Inflammation

The clinical spectrum of asthma is highly variable, and different cellular patterns have been observed, but the presence of airway inflammation remains a consistent feature. The histopathologic features of asthma include inflammatory cell infiltration consisting of eosinophils, lymphocytes, activated mast cells and evidence of injury to epithelial cells. A notable feature of asthma is the presence of mast cells within the bundles of airway smooth muscle. Neutrophils predominate in a subset of patients with asthma including some patients with occupational asthma, those with severe asthma, and patients who smoke, but predominantly neutrophilic inflammation is also found in some patients with none of these characteristics. Based on careful pathology studies in well phenotyped patients, their response to treatment, and overall natural history, asthma is now considered to comprise different subtypes or endotypes in which different aspects of the underlying pathology may dominate the clinical expression of the disease.

Airway Remodeling 

In some patients with asthma persistent changes in airway structure occur, including epithelial goblet cell and submucous gland meta- and hyperplasia, sub-epithelial fibrosis, proliferation of nerves and blood vessels and most importantly, smooth muscle hypertrophy. These changes are not prevented nor completely reversed by currently available therapies, including inhaled corticosteroids. Some patients with asthma develop a phenotype in which airflow obstruction is not completely reversible and is favored by increased severity and duration of asthma and tobacco smoking. It is assumed that this reflects the results of airway remodeling. 

Increasing Prevalence 

There was a sharp increase in the prevalence, morbidity, and mortality associated with asthma beginning in the 1960’s and 1970’s in the so-called “Westernized” countries of the world. A study from Finland indicated a sharp rise in asthma in young adults beginning about 1960, while in Scotland the prevalence of wheezing in school children doubled from 10% to 20% between 1965 and 1989. In the United States, hospitalizations for asthma began to increase in 1972, deaths attributed to asthma began to rise in 1978, while from 1980 to 1994 the prevalence of individuals reporting physician diagnosed asthma increased from 3% to 5.4%, the increase occurring in all age groups, but greater in children.

The best information on the prevalence of asthma throughout the world was obtained by the International Study of Asthma and Allergies in Childhood (ISAAC). Questionnaires were completed primarily in 1994 and 1995 by 463,801 children aged 13-14 years from 56 countries, and by parents of 257,800 children aged 6-7 years from 38 countries. Asthma was considered to be present if there was a positive response to the question “Have you had wheezing or whistling in the chest in the last 12 months”, translated into the appropriate local language. In the 13-14 year old age group, the indicated prevalence varied more than 15-fold between countries, ranging from 2.1%-4.4% in Albania, China, Greece, Georgia, Indonesia, Romania and Russia to 29.1%-32.2% in Australia, New Zealand, Republic of Ireland and the United Kingdom. Other countries with low prevalence were mostly in Asia, Northern Africa, Eastern Europe and the Eastern Mediterranean regions, and others with high prevalence were in South East Asia, North America and Latin America. Trends for prevalence in the 6-7 year olds was similar to those in the older children with prevalence of wheezing varying from 4.1%-32.1%. 

The same survey was conducted 5-10 years later in 56 countries in children 13-14 years of age and 37 countries in children 6-7 years of age. This study, termed ISAAC III, was primarily intended to assess changes in asthma prevalence over time. Overall, there was only a slight increase in asthma prevalence from 13.2% to 13.7% in the 13-14 year olds and from 11.1% to 11.6% in the 6-7 year olds. The most striking change was a decline in prevalence of asthma in the English speaking counties which formerly had had the highest prevalence. Other areas such as Latin American, Eastern Europe and North Africa that already had high to intermediate prevalence continued to show an increase and, with the exception of India, all countries with low prevalence rates in ISAAC I reported increased prevalence in ISAAC III. Thus, overall, the disparity in asthma prevalence found in ISAAC I was found to have diminished, perhaps due to increasing urbanization in developing countries  

An international assessment of the prevalence of asthma in adults (the European Community Respiratory Health Survey or ECRHS) was conducted between 1991 and 1994. Data were obtained on asthma prevalence in 138,565 subjects 20- 44 years of age from 22 countries mostly in Europe, but also Oceania and North America.

There were 15 countries in which both ISAAC and ECRHS data were available and in these countries there was a strong correlation between the two surveys in the finding for current wheeze. Similar to ISAAC, the ECRHS found a high prevalence of reported asthma symptoms in English-speaking countries, and a high prevalence in Western Europe, with a lower prevalence in Eastern and Southern Europe. Overall, the prevalence of reported wheezing in the adults varied from 4.1% to 32%. Factors considered to underlie the increase in asthma are poorly understood even though connections with the Western-type lifestyle seem to be a common factor. Possibilities include diet, air pollution, exposure to certain environmental chemicals and drugs, virus infection, maternal tobacco smoking and changes in housing type and indoor environment. Most likely multiple factors will interact and these may differ in different countries. An important cause of lateonset asthma is chemical exposure in the workplace.